Ophthalmic and Otorhinolaryngological Device Materials

ABSTRACT

Disclosed are soft, high refractive index, acrylic device materials. The materials contain a hydrophilic side-chain macromer for glistening resistance.

This application claims priority to U.S. Provisional Application, U.S.Ser. No. 60/978,000 filed Oct. 5, 2007.

FIELD OF THE INVENTION

This invention is directed to improved ophthalmic andotorhinolaryngological device materials. In particular, this inventionrelates to soft, high refractive index acrylic device materials thathave improved glistening resistance.

BACKGROUND OF THE INVENTION

With the recent advances in small-incision cataract surgery, increasedemphasis has been placed on developing soft, foldable materials suitablefor use in artificial lenses. In general, these materials fall into oneof three categories: hydrogels, silicones, and acrylics.

In general, hydrogel materials have a relatively low refractive index,making them less desirable than other materials because of the thickerlens optic necessary to achieve a given refractive power. Conventionalsilicone materials generally have a higher refractive index thanhydrogels, but tend to unfold explosively after being placed in the eyein a folded position. Explosive unfolding can potentially damage thecorneal endothelium and/or rupture the natural lens capsule. Acrylicmaterials are desirable because they typically have a high refractiveindex and unfold more slowly or controllably than conventional siliconematerials.

U.S. Pat. No. 5,290,892 discloses high refractive index, acrylicmaterials suitable for use as an intraocular lens (“IOL”) material.These acrylic materials contain, as principal components, two arylacrylic monomers. The IOLs made of these acrylic materials can be rolledor folded for insertion through small incisions.

U.S. Pat. No. 5,331,073 also discloses soft acrylic IOL materials. Thesematerials contain as principal components, two acrylic monomers whichare defined by the properties of their respective homopolymers. Thefirst monomer is defined as one in which its homopolymer has arefractive index of at least about 1.50. The second monomer is definedas one in which its homopolymer has a glass transition temperature lessthan about 22° C. These IOL materials also contain a cross-linkingcomponent. Additionally, these materials may optionally contain a fourthconstituent, different from the first three constituents, which isderived from a hydrophilic monomer. These materials preferably have atotal of less than about 15% by weight of a hydrophilic component.

U.S. Pat. No. 5,693,095 discloses foldable, high refractive indexophthalmic lens materials containing at least about 90 wt. % of only twoprincipal components: one aryl acrylic hydrophobic monomer and onehydrophilic monomer. The aryl acrylic hydrophobic monomer has theformula

wherein:

-   -   X is H or CH₃;    -   m is 0-6;    -   Y is nothing, O, S, or NR, wherein R is H, CH₃, C_(n)H_(2n+1)        (n=1-10), iso-OC₃H₇, C₆H₅, or CH₂C₆H₅; and    -   Ar is any aromatic ring which can be unsubstituted or        substituted with CH₃, C₂H₅, n-C₃H₇, iso-C₃H₇, OCH₃, C₆H₁₁, Cl,        Br, C₆H₅, or CH₂C₆H₅.        The lens materials described in the '095 Patent preferably have        a glass-transition temperature (“T_(g)”) between about −20 and        +25° C.

Flexible intraocular lenses may be folded and inserted through a smallincision. In general, a softer material may be deformed to a greaterextent so that it can be inserted through an increasingly smallerincision. Soft acrylic or methacrylic materials typically do not have anappropriate combination of strength, flexibility and non-tacky surfaceproperties to permit IOLs to be inserted through an incision as small asthat required for silicone IOLs.

Polyethylene glycol (PEG) dimethacrylates are known to improveglistening resistance of hydrophobic acrylic formulations. See, forexample, U.S. Pat. Nos. 5,693,095; 6,528,602; 6,653,422; and 6,353,069.Both the concentration and molecular weight of PEG dimethacrylates havean impact on glistening performance. Generally, use of higher molecularweight PEG dimethacrylates (1000 MW) yield copolymers with improvedglistening performance at low PEG concentrations (10-15 wt %), ascompared to lower molecular weight PEG dimethacrylates (<1000 MW).However, low PEG dimethacrylate concentrations are desirable to maintaina high refractive index copolymer. Addition of PEG dimethacrylates alsotends to decrease the modulus and tensile strength of the resultingcopolymer. Also, higher molecular weight PEG dimethacrylates aregenerally not miscible with hydrophobic acrylic monomers.

SUMMARY OF THE INVENTION

Improved soft, foldable acrylic device materials which are particularlysuited for use as IOLs, but which are also useful as other ophthalmic orotorhinolaryngological devices, such as contact lenses,keratoprostheses, corneal rings or inlays, otological ventilation tubesand nasal implants, have been discovered. These polymeric materialscomprise macromers containing hydrophilic side-chains.

The subject hydrophilic side-chain macromers allow synthesis ofglistening resistant, low equilibrium water content, high refractiveindex IOLs. The use of a macromer having a hydrophilic side-chain allowsincorporation of higher molecular weight hydrophilic ingredients into ahydrophobic copolymer formulation. Higher molecular weight hydrophilicingredients are more efficient glistening resistance ingredients thancomparable weight fractions of lower molecular weight hydrophilicpolymers. This resulting hydrophilic ingredient concentration reductionresults in reduced equilibrium water content, higher refractive index,and a smaller mass intraocular lens that can be inserted through asmaller incision.

DETAILED DESCRIPTION OF THE INVENTION

Unless indicated otherwise, all component amounts are presented on a %(w/w) basis (“wt. %”).

The device materials of the present invention are copolymers comprisinga) a monofunctional acrylate or methacrylate monomer [1], b) adifunctional acrylate or methacrylate cross-linker [2], and c) ahydrophilic side-chain macromer [3] (which may be a macromer of formula[3a], [3b], [3c], [3d], or [3e]). The device materials may contain morethan one monomer [1], more than one monomer [2], and more than onemacromer [3]. Unless indicated otherwise, references to each ingredientare intended to encompass multiple monomers or macromers of the sameformula and references to amounts are intended to refer to the totalamount of all monomers of each formula.

wherein

-   -   B=—O(CH₂)_(n)—, —(OCH₂CH₂)_(n)—, —NH(CH₂)_(n)—, or        —NCH₃(CH₂)_(n)—;    -   R¹=H, CH₃, CH₂CH₃, or CH₂OH;    -   n=0-12;    -   A=C₆H₅ or O(CH₂)_(m)C₆H₅, where the C₆H₅ group is optionally        substituted with —(CH₂)_(n)H, —O(CH₂)_(n)H, —CH(CH₃)₂, —C₆H₅,        —OC₆H₅, —CH₂C₆H₅, F, Cl, Br, or I; and    -   m=0-18;

wherein

-   -   R², R³ independently=H, CH₃, CH₂CH₃, or CH₂OH;    -   W, W′ independently=O(CH₂)_(d), NH(CH₂)_(d), NCH₃(CH₂)_(d),        O(CH₂)_(d)C₆H₄, O(CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂O)_(d)CH₂,        O(CH₂CH₂CH₂CH₂O)_(d)CH₂, or nothing;    -   J=(CH₂)_(a), O(CH₂CH₂O)_(b), O, or nothing, provided that if W        and W′=nothing, then J≠nothing;    -   d=0-12;    -   a=1-12;    -   b=1-24;

wherein for formulas [3a], [3b], [3c], [3d], and [3e] (collectively,“formula [3]”)

-   -   e=1-50;    -   X=—O—, NH—, —N(CH₃)—, —N(CH₂CH₃)—, or —N(C₆H₅)—;    -   Y=—H, —(CH₂)_(p)OH, —CH₂CH₂N(CH₃)₂, —CH₂CH₂N(CH₂CH₃)₂,        —CH₂CH(OH)CH₂OH, —(CH₂CH₂O)_(q)CH₃, —(CH₂CH₂O)_(g)H,        —(CH₂CH₂O)_(q)C₆H₅, or

-   -   p=1-12;    -   q=1-230;    -   T, T′ independently=O(CH₂)_(d′), NH(CH₂)_(d′), NCH₃(CH₂)_(d′),        O(CH₂)_(d′)C₆H₄, O(CH₂CH₂O)_(d′)CH₂, O(CH₂CH₂CH₂O)_(d′)CH₂,        O(CH₂CH₂CH₂CH₂O)_(d)—H₂, or nothing;    -   K=(CH₂)_(a′), O(CH₂CH₂O)_(b′), O, or nothing, provided that if T        and T′=nothing, then K≠nothing;    -   d′=0-12;    -   a′=1-12;    -   b′=1-24;    -   L=H, Cl, Br, —CH₂C(O)CH₃, CH₂C(O)C(CH₃)₃, —CH₂C(O)C₆H₅,        —CH₂C(O)C₆H₄OH, —CH₂C(O)C₆H₄OCH₃,

-   -    or —CH₂CH═CH₂;    -   R⁴, R⁵ independently=H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,        CH₂CH₂CH₂CH₃, or CH₂CH(CH₃)₂;    -   R₆=—CO₂CH₃, —CO₂CH₂CH₃, —CN, or —CONHCH₂CH₂CH₂CH₃;    -   R⁷, R⁸ independently=H, CH₃, CH₂CH₃, or CH₂OH;    -   M=—(CH₂)_(a″)—; and    -   a″=2-20.

Preferred monomers of formula [1] are those wherein:

-   -   B=—O(CH₂)_(n)— or —(OCH₂CH₂)_(n)—;    -   R¹=—H or —CH₃;    -   n=1-5;    -   A=—C₆H₅, O(CH₂)_(m)C₆H₅; and    -   m=0-4.

Preferred monomers of formula [2] are those wherein:

-   -   R², R³ independently=H or CH₃;    -   W, W′ independently=O(CH₂)_(d), O(CH₂)_(d)C₆H₄, or nothing;    -   J=O(CH₂CH₂O)_(b) or nothing, provided that if W and W′=nothing,    -   then J≠nothing;    -   d=0-6; and    -   b=1-10.

Preferred macromers of formula [3] are those wherein:

-   -   e=2-40;    -   X=—O— or —N(CH₃)—;    -   Y=(CH₂CH₂O)_(q)CH₃, —(CH₂CH₂O)_(q)H, or —(CH₂CH₂O)_(q)C₆H₅;    -   q=2-23;    -   T, T′ independently=O(CH₂)_(d′) or nothing;    -   K=O(CH₂CH₂O)_(b′) or nothing, provided that if T and T′=nothing,        then    -   K≠nothing;    -   d′=0-6;    -   b′=1-10;    -   L=H, Cl, Br, —CH₂C(O)C₆H₅, —CH₂C(O)C₆H₄OH, —CH₂C(O)C₆H₄OCH₃, or        —CH₂CH═CH₂;    -   R⁴, R⁵ independently=H, CH₃, or CH₂CH₃;    -   R₆=—CO₂CH₃, —CO₂CH₂CH₃, —CN, or —CONHCH₂CH₂CH₂CH₃;    -   R⁷, R⁸ independently=H or CH₃; and    -   a″=2-12.

Most preferred macromers of formula [3] are those wherein:

-   -   e=5-30;    -   X=—O—;    -   Y=(CH₂CH₂O)_(q)CH₃;    -   q=4-15;    -   T, T′ independently=O(CH₂)_(d′), O(CH₂)_(d)′C₆H₄, or nothing;    -   K=O(CH₂CH₂O)_(b′) or nothing, provided that if T and T′=nothing,        then    -   K≠nothing;    -   d′=0-6;    -   b′=1-10;    -   L=H, —CH₂C(O)C₆H₅, —CH₂C(O)C₆H₄OCH₃, or —CH₂CH═CH₂;    -   R⁴, R⁵ independently=H, CH₃, or CH₂CH₃;    -   R₆=—CO₂CH₃, —CO₂CH₂CH₃, —CN, or —CONHCH₂CH₂CH₂CH₃;    -   R⁷, R⁸ independently=H or CH₃; and    -   a″=2-12.

Monomers of formula [1] are known and can be made by known methods. See,for example, U.S. Pat. Nos. 5,331,073 and 5,290,892. Many monomers offormula [1] are commercially available from a variety of sources.Preferred monomers of formula [1] include benzyl methacrylate;2-phenylethyl methacrylate; 3-phenylpropyl methacrylate; 4-phenylbutylmethacrylate; 5-phenylpentyl methacrylate; 2-phenoxyethyl methacrylate;2-(2-phenoxyethoxy)ethyl methacrylate; 2-benzyloxyethyl methacrylate;2-(2-(benzyloxy)ethoxy)ethyl methacrylate; and 3-benzyloxypropylmethacrylate; and their corresponding acrylates.

Monomers of formula [2] are known and can be made by known methods. Manyare commercially available. Preferred monomers of formula [2] includeethylene glycol dimethacrylate; diethylene glycol dimethacrylate;triethylene glycol dimethacrylate; 1,6-hexanediol dimethacrylate;1,4-butanediol dimethacrylate; 1,4-benzenedimethanol dimethacrylate; andtheir corresponding acrylates. Most preferred is 1,4-butanedioldiacrylate.

Macromers of formula [3] can be made by known methods. They arecommercially available in some instances and can be made by knownmethods. Macromonomers of formula [3] can be made by covalentlyattaching a polymerizable group to a functional end group of a linear orbranched acrylic or methacrylic polymer. For example, a hydroxylterminated poly(alkyl methacrylate) may be synthesized by anionicpolymerization using an initiator containing a protected hydroxyl group,that following deprotection, is reacted with, for example, methacryloylchloride or methacrylic acid to produce macromer [3a]. The terminalhydroxyl group may also be reacted with other reagents, for exampleisocyanatoethyl methacrylate or vinyl benzyl chloride, to produce aterminal polymerizable group. See, generally, U.S. Pat. Nos. 6,221,991,3,862,077 and 3,842,059, the entire contents of which are incorporatedby reference. Alternatively, the polymerization may be terminated withan aldehyde and subsequently reacted with methacryloyl chloride toproduce functional macromer [3b] (See for example, U.S. Pat. Nos.6,221,991 and 5,391,628).

Macromers of formula [3c] can also be prepared using atom transferradical polymerization (ATRP) conditions. For example, a hydroxylterminal initiator (hydroxyethyl bromoisobutyrate) can combined withcopper(I) halide and a solubilizing amine ligand. This can be used toinitiate the polymerization of an acrylate or methacrylate monomer. Theresulting hydroxyl terminated poly(acrylate) or poly(methacrylate) canthen be reacted with methacryloyl chloride or isocyanatoethylmethacrylate. See, generally, U.S. Pat. Nos. 5,852,129, 5,763,548, and5,789,487, and Neugebauer, et al., “Densely-grafted and double-graftedPEO brushes via ATRP. A route to soft elastomers,” Macromolecules 2003,36, 6746-6755; Ishizu, et al., “Aggregation behaviors of AB-typebrush-block-brush amphiphilic copolymers in aqueous media,” Journal ofMaterials Science 2004, 39, 4295-4300; Kurjata, et al., “Synthesis ofpoly[dimethylsiloxane-block-oligo(ethylene glycol) methyl ethermethacrylate]: an amphiphilic copolymer with a comb-like block,” Polymer2004, 45, 6111-6121; and Wang, et al., “Facile Atom Transfer RadicalPolymerization of Methoxy-Capped Oligo(ethylene glycol) Methacrylate inAqueous Media at Ambient Temperature,” Macromolecules 2000, 33,6640-6647. Alternatively, a catalytic chain transfer reagent may be usedin conjunction with living polymerization techniques to producemethacrylic macromonomers of formula [3d]. See for example Norman, J. etal. Macromolecules 2002, 35, 8954-8961, or Bon, S. A. F. et al. J.Polym. Sci., Polym. Chem. 2000, 38, 2678. Macromers of formula [3e] maybe produced, for example, by polymerization in the presence of a thiolfunctional chain transfer agent followed by reaction with methacryloylchloride or isocyanatoethyl methacrylate. For example, see Chen, G.-F.et al. Macromolecules 1991, 24, 2151.

The copolymeric materials of the present invention contain a totalamount of monomer [1] in an amount from 70 to 98%, preferably from 80 to95%. The difunctional cross-linker [2] concentration can be on the orderof 0.5 to 3% of the total concentration, and preferably from 1 to 2%.

The materials of the present invention have at least one macromer of[3]. The total amount of macromer [3] depends on the desired physicalproperties for the device materials. The copolymeric materials of thepresent invention contain a total of at least 0.5 wt % and can containas much as 15% of macromer [3]. Preferably, the copolymeric devicematerials will contain 1-10 wt % of macromer [3]. More preferably, thedevice materials will contain 1-5 wt % of macromer [3]. Most preferably,the device materials will contain 2-4 wt % of macromer [3].

The copolymeric device materials of the present invention optionallycontain one or more ingredients selected from the group consisting ofpolymerizable UV absorbers and polymerizable colorants. Preferably, thedevice material of the present invention contains no other ingredientsbesides the monomers of formulas [1] and [2], the macromer [3], and theoptional polymerizable UV absorbers and polymerizable colorants.

Reactive UV absorbers are known. A suitable reactive UV absorber is2-(2′-hydroxy-3′-methallyl-5′-methylphenyl)benzotriazole, commerciallyavailable as o-Methallyl Tinuvin P (“oMTP”) from Polysciences, Inc.,Warrington, Pennsylvania. UV absorbers are typically present in anamount from about 0.1-5%. Suitable reactive blue-light absorbingcompounds include those described in U.S. Pat. No. 5,470,932. Blue-lightabsorbers are typically present in an amount from about 0.01-0.5%. Whenused to make IOLs, the device materials of the present inventionpreferably contain both a reactive UV absorber and a reactive colorant.

In order to form the device material of the present invention, thechosen ingredients [1], [2], and [3], along with any of the optionalingredients, are combined and polymerized using a radical initiator toinitiate polymerization by the action of either heat or radiation. Thedevice material is preferably polymerized in de-gassed polypropylenemolds under nitrogen or in glass molds.

Suitable polymerization initiators include thermal initiators andphotoinitiators. Preferred thermal initiators include peroxyfree-radical initiators, such as t-butyl (peroxy-2-ethyl)hexanoate anddi-(tert-butylcyclohexyl) peroxydicarbonate (commercially available asPerkadox® 16 from Akzo Chemicals Inc., Chicago, Ill.). Particularly incases where the materials of the present invention do not contain ablue-light absorbing chromophore, preferred photoinitiators includebenzoylphosphine oxide initiators, such as2,4,6-trimethyl-benzoyldiphenyl-phosphine oxide, commercially availableas Lucirin® TPO from BASF Corporation (Charlotte, N.C.). Initiators aretypically present in an amount equal to about 5% or less of the totalformulation weight, and more preferably less than 2% of the totalformulation. As is customary for purposes of calculating componentamounts, the initiator weight is not included in the formulation weight% calculation.

The particular combination of the ingredients described above and theidentity and amount of any additional components are determined by thedesired properties of the finished device material. In a preferredembodiment, the device materials of the present invention are used tomake IOLs having an optic diameter of 5.5 or 6 mm that are designed tobe compressed or stretched and inserted through surgical incision sizesof 2 mm or less. For example, the macromonomer [3] is combined with amono-functional acrylate or methacrylate monomer [1], a multifunctionalacrylate or methacrylate cross-linker [2], a reactive UV absorber and areactive colorant and copolymerized using a radical initiator in asuitable lens mold.

The device material preferably has a refractive index in the hydratedstate of at least about 1.50, and more preferably at least about 1.53,as measured by an Abbe' refractometer at 589 nm (Na light source) and25° C. Optics made from materials having a refractive index lower than1.50 are necessarily thicker than optics of the same power which aremade from materials having a higher refractive index. As such, IOLoptics made from materials with comparable mechanical properties and arefractive index lower than about 1.50 generally require relativelylarger incisions for IOL implantation.

The proportions of the monomers and macromer to be included in thecopolymers of the present invention should be chosen so that thecopolymer has a glass transition temperature (T_(g)) not greater thanabout 37° C., which is normal human body temperature. Copolymers havingglass transition temperatures higher than 37° C. are not suitable foruse in foldable IOLs; such lenses could only be rolled or folded attemperatures above 37° C. and would not unroll or unfold at normal bodytemperature. It is preferred to use copolymers having a glass transitiontemperature somewhat below normal body temperature and no greater thannormal room temperature, e.g., about 20-25° C., in order that IOLs madeof such copolymers can be rolled or folded conveniently at roomtemperature. T_(g) is measured by differential scanning calorimetry at10° C./min., and is determined at the midpoint of the transition of theheat flux curve.

For IOLs and other applications, the materials of the present inventionmust exhibit sufficient strength to allow devices made of them to befolded or manipulated without fracturing. Thus the copolymers of thepresent invention will have an elongation of at least 80%, preferably atleast 100%, and most preferably greater than 110%. This propertyindicates that lenses made of such materials generally will not crack,tear or split when folded. Elongation of polymer samples is determinedon dumbbell shaped tension test specimens with a 20 mm total length,length in the grip area of 4.88 mm, overall width of 2.49 mm, 0.833 mmwidth of the narrow section, a fillet radius of 8.83 mm, and a thicknessof 0.9 mm. Testing is performed on samples at ambient conditions usingan Instron Material Tester (Model No. 4442 or equivalent) with a 50Newton load cell. The grip distance is set at 14 mm and a crossheadspeed is set at 500 mm/minute and the sample is pulled until failure.The elongation (strain) is reported as a fraction of the displacement atfailure to the original grip distance. Since the materials to be testedare essentially soft elastomers, loading them into the Instron machinetends to make them buckle. To remove the slack in the material sample apre-load is placed upon the sample. This helps to reduce the slack andprovide a more consistent reading. Once the sample is pre-loaded to adesired value (typically 0.03 to 0.05 N) the strain is set to zero andthe test begun. The modulus is calculated as the instantaneous slope ofthe stress-strain curve at 0% strain (“Young's modulus”), 25% strain(“25% modulus”) and 100% strain (“100% modulus).

IOLs made of the ophthalmic device materials of the present inventionare more resistant to glistenings than other materials. Glistenings aremeasured according to the following test. The presence of glistenings ismeasured by placement of a lens or disk sample into a vial or sealedglass chamber and adding deionized water or a balanced salt solution.The vial or glass chamber is then placed into a water bath preheated to45° C. Samples are to be maintained in the bath for a minimum of 16hours and preferably 24±2 hours. The vial or glass chamber is thencooled to ambient temperature for a minimum of 60 minutes and preferably90±30 minutes. The sample is inspected visually in various on angle oroff angle lighting to evaluate clarity. Visualization of glistenings iscarried out at ambient temperature with a light microscope using amagnification of 50 to 200×. A sample is judged to have many glisteningsif, at 50-200× magnification, there are approximately 50 to 100% as manyglistenings as observed in control samples based on 65 weight %2-phenylethyl acrylate, 30 weight % 2-phenylethyl methacrylate, 3.2weight % 1,4-butanediol diacrylate, and 1.8 weight % oMTP. Similarly, asample is judged to have few glistenings if there are approximately 10%or more glistenings relative to the quantity observed in controlsamples. A sample is judged to have very few glistenings if there areapproximately 1% or more glistenings relative to a control sample. Asample is judged to be free of glistenings if the number of glisteningsdetected in the eyepiece is zero. A sample is judged to be substantiallyfree of glistenings if, at 50-200× magnification, the number ofglistenings detected in the eyepiece is less than about 2/mm³. It isoften very difficult to detect glistenings, especially at surfaces andedges where more defects and debris have formed, so the sample israstered throughout the entire volume of the lens, varying themagnification levels (50-200×), the aperture iris diaphragm, and thefield conditions (using both bright field and dark field conditions) inan attempt to detect the presence of glistenings.

The copolymers of the present invention most preferably have anequilibrium water content (EWC) of 0.5-3.0%. EWC may be gravimetricallydetermined by comparison of dry and hydrated sample weight. First, thedry sample weight is obtained, then the sample is placed in a suitablecontainer and equilibrated in de-ionized H₂O at a prescribed temperaturefor at least 24 h. The sample is then removed from the de-ionized H₂O,excess surface water is removed and the sample is weighed. EWC isdetermined by the following formula: %EWC=[(wt_(hyd)−wt_(dry))/wt_(hyd)]×100

IOLs constructed of the device materials of the present invention can beof any design capable of being stretched or compressed into a smallcross section that can fit through a 2-mm incision. For example, theIOLs can be of what is known as a one-piece or multi-piece design, andcomprise optic and haptic components. The optic is that portion whichserves as the lens and the haptics are attached to the optic and arelike arms that hold the optic in its proper place in the eye. The opticand haptic(s) can be of the same or different material. A multi-piecelens is so called because the optic and the haptic(s) are madeseparately and then the haptics are attached to the optic. In a singlepiece lens, the optic and the haptics are formed out of one piece ofmaterial. Depending on the material, the haptics are then cut, orlathed, out of the material to produce the IOL.

In addition to IOLs, the materials of the present invention are alsosuitable for use as other ophthalmic or otorhinolaryngological devicessuch as contact lenses, keratoprostheses, corneal inlays or rings,otological ventilation tubes and nasal implants.

The invention will be further illustrated by the following examples,which are intended to be illustrative, but not limiting.

Example 1

All monomers, cross-linkers and initiators were purchased fromcommercial sources. Macromer [3] (“polyPEG-MA”) was synthesized frompoly(ethylene glycol) 550 monomethyl ether monomethacrylate (“PEG-MA550”). Two macromer [3] molecular weights were used: “polyPEG-MA 4.1k”(GPC M_(n) 4,112; M_(w)/M_(n) of 1.80; e=7 (calculated as 4112/550)) and“polyPEG-MA 10.3 k” (GPC M_(n) 10,300; M_(w)/M_(n) of 1.44; e=19).2-phenylethyl methacrylate (PEMA) and benzyl methacrylate (BzMA) wereeach passed through basic alumina and degassed with N₂ prior to use.2-Phenylethyl acrylate (“PEA”), benzyl acrylate (“BzA”), and1,4-butanediol diacrylate is (“BDDA”) were purified by columnchromatography prior to use. 2,2-Azobisisobutyronitrile (“AIBN”) wasrecrystallized from methanol prior to use.Di-(4-t-butylcyclohexyl)peroxydicarbonate (“Perkadox® 16S”),2-(2′-Hydroxy-3′-t-butyl-5′-(3″-(2′″-hydroxy-3′″-methacryloyloxypropoxy)propoxy)phenyl)-5-methoxy-2H-benzotriazole(“UV13”), and ortho-methallyl Tinuvin®P (“oMTP”) were used as received.

Polypropylene molds were vacuum de-gassed at 90° C. prior to use. Themolds were placed in a nitrogen atmosphere glove box immediately afterdegassing. The monomer(s), macromer, and cross-linker were combined asindicated in Table 1. AIBN or Perkadox®16S initiator was added (0.5-2.0wt. %), the solution was mixed thoroughly then placed under low vacuumto remove any trapped air bubbles, back-flushed with nitrogen, andimmediately placed in the glove box. The monomer formulation wasdispensed into vacuum de-gassed polypropylene molds using a syringeequipped with a 0.2 μm PTFE filter. The filled molds were placed in aconvection oven for 1 hr at 70° C., then 2 hrs at 110° C. The resultingpolymer samples were removed from the molds and extracted in refluxingacetone for 6 hours, rinsed and air dried, then placed under vacuum at70° C. for at least 15 hrs. Tensile properties, T_(g), EWC, glisteningresistance, and refractive index were determined according to themethods described above. The results are listed in Table 2.

TABLE 1 Formulation Component Detail PolyPEG- PolyPEG- PEA BzA PEMA BzMABDDA UV13 oMTP MA 4.1k MA 10.3k ID (wt %) (wt %) (wt %) (wt %) (wt %)(wt %) (wt %) (wt %) (wt %) 0 65.0 — 30.0 — 3.2 — 1.8 0.0 — 1 63.1 —29.1 — 3.1 — 1.7 3.0 — 2 61.1 — 28.2 — 3.0 — 1.7 6.0 — 3 59.2 — 27.3 —2.9 — 1.6 9.0 — 4 89.00 — — — 1.00 — — 10.00 — 5 78.99 — — — 1.00 — —20.00 — 6 67.48 — 20.00 10.00  1.52 — — 1.01 — 7 66.47 — 19.99 10.00 1.52 — — 2.02 — 8 65.48 — 19.99 9.99 1.52 — — 3.01 — 9 64.47 — 20.029.99 1.51 — — 4.00 — 10 63.50 — 19.99 10.00  1.50 — — 5.01 — 11 — 97.99— — 1.01 — — 1.00 — 12 10.00 88.01 — — 1.00 — — 1.00 — 13 — 96.50 — —1.50 — — 2.00 — 14 — 95.49 — — 1.50 — — 3.02 — 15 — 95.98 — — 2.00 — —2.02 — 16 — 94.96 — — 2.03 — — 3.01 — 17 — 90.48 — 5.00 1.50 — — 3.02 —18 — 95.47 — — 1.51 — — — 3.02 19 — 93.46 — 2.01 1.51 — — 3.03 — 20 —93.24 — 2.25 1.51 — — 3.00 — 21 — 92.49 — 3.01 1.51 — — 3.00 — 22 —91.47 — 4.00 1.51 — — 3.01 — 23 — 87.99 — 7.50 1.51 — — 3.00 — 24 —85.49 — 10.01  1.50 — — 3.00 — 25 — 83.68 — 10.01  1.50 1.80 — 3.00 —

TABLE 2 Tensile and Thermal Properties, % EWC and Glistening TestResults Tensile Strain at Young's 100% Secant RI Strength Break ModulusModulus EWC (22° C., ID (MPa) (MPa) (MPa) (MPa) (%) Glistenings T_(g) (°C.) dry) 0 8.12 104 57.30 7.51 0.30 Many 9.5 — 1 8.34 114 40.87 6.390.66 None 6.6 1.5537 2 6.23 110 19.89 4.94 1.68 None 2.4 1.5513 3 — — —— 2.69 None −0.9   1.5480 4 1.56 163  1.56 0.65 3.92 None — 1.5457 50.92 132  1.02 0.63 9.78 None — 1.5375 6 8.53 174 48.07 3.63 0.50 Few —1.5562 7 8.57 177 37.57 3.22 0.75 None 7.5 1.5553 8 7.65 173 28.43 2.781.00 None — 1.5545 9 7.39 174 23.99 2.52 1.32 None — 1.5536 10 6.42 16718.53 2.27 1.61 None — 1.5528 11 9.77 252 39.94 2.20 0.46 Few — 1.564412 8.53 246 25.62 1.73 0.48 Few — 1.5633 13 6.20 183 12.90 1.62 0.85Very Few — 1.5633 14 6.24 183 10.25 1.51 1.10 None — 1.5621 15 6.91 16012.39 2.11 0.81 Very Few — 1.5630 16 6.69 158 11.64 2.10 1.06 None —1.5615 17 10.73  201 56.72 3.40 0.89 None — 1.5620 18 9.41 197 38.552.72 1.37 Very Few — 1.5610 19 8.91 190 38.54 2.75 1.08 None — 1.5620 208.91 190 30.52 2.39 0.91 None — — 21 9.60 192 45.32 2.95 1.02 None —1.5622 22 9.86 191 50.74 3.19 1.00 None — 1.5622 23 9.70 184 56.25 3.561.25 None — — 24 10.29  184 62.28 4.03 1.06 None  13.347 — 25 — — — —0.93 None — 1.5636

Example 2

The copolymers shown in Table 3, which contained varying sizes ofPEG-containing additive (PEG-MA 550, PolyPEG-MA 4.1k, and PoIyPEG-MA10.3k), were prepared in the manner described in Example 1. Tensileproperties, EWC, glistening resistance, and refractive index weredetermined according to the methods described above. The results arelisted in Table 4.

TABLE 3 Comparative Examples Formulation Component Detail BzA BDDAPEG-MA PolyPEG-MA PolyPEG-MA ID (wt %) (wt %) 550 (wt %) 4.1k (wt %)10.3k (wt %) 26 93.47 1.51 5.02 — — 27 93.47 1.51 — 5.02 — 28 93.49 1.51— — 5.00

TABLE 4 Comparative Formulation Tensile and Thermal Properties, % EWCand Glistening Test Results 100% Tensile Strain at Young's Secant RIStrength Break Modulus Modulus EWC Glisten- (22° C., ID (MPa) (MPa)(MPa) (MPa) (%) ings dry) 26 6.87 191 12.79 1.64 0.59 Many 1.5598 277.49 189 16.25 1.85 1.50 None 1.5604 28 8.92 199 25.32 2.22 2.35 None1.5595

Example 3

The copolymers shown in Table 5, which contained varying molecularweights of the polyPEG-MA additive: “polyPEG-MA 3570” (GPC M_(n) 3570;M_(w)/M_(n) of 1.42; e=6), “polyPEG-MA 4012” (GPC M_(n) 4012;M_(w)/M_(n) 1.54; e=7), “polyPEG-MA 4141” (GPC M_(n) 4141; M_(w)/M_(n)1.50; e=8), and polyPEG-MA 3708 (GPC M_(n) 3708; M_(w)/M_(n) 1.49; e=7)were prepared in the manner described in Example 1. Tensile properties,EWC, glistening resistance, and refractive index were determinedaccording to the methods described above. The results are listed inTable 6.

TABLE 5 Formulation Component Detail PEG-MA PolyPEG- PolyPEG- PolyPEG-PolyPEG- BzA BzMA BDDA 550 MA 3570 MA 4012 MA 4141 MA 3708 ID (wt %) (wt%) (wt %) (wt %) (wt %) (wt %) (wt %) (wt %) 29 85.47 9.99 1.52 3.02 — —— — 30 83.46 9.99 1.51 5.03 — — — — 31 78.49 10.01 1.50 10.00 — — — — 3273.50 10.00 1.51 15.00 — — — — 33 68.50 10.00 1.50 20.00 — — — — 3485.46 10.00 1.53 — 3.00 — — — 35 83.47 10.02 1.50 — 5.01 — — — 36 85.389.99 1.61 — — 3.02 — — 37 85.47 10.00 1.50 — — — 3.03 — 38 85.40 10.011.52 — — — — 3.07

TABLE 6 Tensile and Thermal Properties, % EWC and Glistening TestResults 100% Tensile Strain at Young's Secant RI Strength Break ModulusModulus EWC Glisten- (22° C., ID (MPa) (MPa) (MPa) (MPa) (%) ings dry)29 8.26 175 38.99 3.42 0.46 Many 1.5631 30 6.67 170 18.07 2.33 0.55 Many1.5611 31 3.94 151 9.25 1.51 0.79 Few 1.5566 32 2.79 134 6.44 1.42 1.19Very 1.5518 Few 33 2.41 126 2.59 1.47 3.38 None 1.5493 34 8.23 167 46.353.94 0.74 None 1.5630 35 7.47 169 26.69 3.04 1.21 None 1.5608 36 8.60163 45.02 4.29 0.88 None 1.5626 37 8.19 167 45.24 4.04 0.90 None 1.562738 8.94 173 44.30 4.07 0.79 None 1.5626

This invention has been described by reference to certain preferredembodiments; however, it should be understood that it may be embodied inother specific forms or variations thereof without departing from itsspecial or essential characteristics. The embodiments described aboveare therefore considered to be illustrative in all respects and notrestrictive, the scope of the invention being indicated by the appendedclaims rather than by the foregoing description.

1-21. (canceled)
 22. A polymeric ophthalmic or otorhinolaryngologicaldevice material comprising a) 70 to 98% (w/w) of a monofunctionalacrylate or methacrylate monomer of formula [1]:

wherein B=—O(CH₂)_(n)—, —(OCH₂CH₂)_(n)—, —NH(CH₂)_(n)—, or—NCH₃(CH₂)_(n)—; R¹=H, CH₃, CH₂CH₃, or CH₂OH; n=0-12; A=C₆H₅ orO(CH₂)_(m)C₆H₅, where the C₆H₅ group is optionally substituted with—(CH₂)_(n)H, —O(CH₂)_(n)H, —CH(CH₃)₂, —C₆H₅, —OC₆H₅, —CH₂C₆H₅, F, Cl,Br, or I; and m=0-18; b) a difunctional acrylate or methacrylatecross-linking monomer of formula [2]:

wherein R², R³ independently=H, CH₃, CH₂CH₃, or CH₂OH; W, W′independently=O(CH₂)_(d), NH(CH₂)_(d), NCH₃(CH₂)_(d), O(CH₂)_(d)C₆H₄,O(CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂CH₂O)_(d)CH₂, ornothing; J=(CH₂)_(a), O(CH₂CH₂O)_(b), O, or nothing, provided that if Wand W′=nothing, then J≠nothing; d=0-12; a=1-12; and b=1-24; and c) 0.5to 15% (w/w) of a hydrophilic side-chain macromer of formula [3c]:

wherein for formula [3c]: e=1-50; X=—O—, NH—, —N(CH₃)—, —N(CH₂CH₃)—, or—N(C₆H₅)—; Y=—H, —(CH₂)_(p)OH, —CH₂CH₂N(CH₃)₂, —CH₂CH₂N(CH₂CH₃)₂,—CH₂CH(OH)CH₂OH, —(CH₂CH₂O)_(p)CH₃, —(CH₂CH₂O)_(p)H, —(CH₂CH₂O)_(q)C₆H₅,or

p=1-12; q=1-230; T, T′ independently=O(CH₂)_(d′), NH(CH₂)_(d′),NCH₃(CH₂)_(d′), O(CH₂)_(d′)C₆H₄, O(CH₂CH₂O)_(d′)CH₂,O(CH₂CH₂CH₂O)_(d′)CH₂, O(CH₂CH₂CH₂CH₂O)_(d′)CH₂, or nothing; K=NHC(O)O;d′=0-12; L=H, Cl, Br, —CH₂C(O)CH₃, CH₂C(O)C(CH₃)₃, —CH₂C(O)C₆H₅,—CH₂C(O)C₆H₄OH, —CH₂C(O)C₆H₄OCH₃,

 or —CH₂CH═CH₂; R⁴, R⁵ independently=H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, or CH₂CH(CH₃)₂; and R⁷, R⁸ independently=H, CH₃,CH₂CH₃, or CH₂OH.
 23. The polymeric device material of claim 22 whereinfor the monomer of formula [1]: B=—O(CH₂)_(n)— or —(OCH₂CH₂)_(n)—; R¹=—Hor —CH₃; n=1-5; A=—C₆H₅, O(CH₂)_(m)C₆H₅; and m=0-4.
 24. The polymericdevice material of claim 22 wherein for the monomer of formula [2]: R²,R³ independently=H or CH₃; W, W′ independently=O(CH₂)_(d),O(CH₂)_(d)C₆H₄, or nothing; J=O(CH₂CH₂O)_(b) or nothing, provided thatif W and W′=nothing, then J≠nothing; d=0-6; and b=1-10.
 25. Thepolymeric device material of claim 22 wherein for the macromer offormula [3c]: e=2-40; X=—O— or —N(CH₃)—; Y=(CH₂CH₂O)_(q)CH₃,—(CH₂CH₂O)_(q)H, or —(CH₂CH₂O)_(q)C₆H₅; q=2-23; T, T′independently=O(CH₂)_(d′) or nothing; d′=0-6; L=H, Cl, Br, —CH₂C(O)C₆H₅,—CH₂C(O)C₆H₄OH, —CH₂C(O)C₆H₄OCH₃, or —CH₂CH═CH₂; R⁴, R⁵ independently=H,CH₃, or CH₂CH₃; and R⁷, R⁸ independently=H or CH₃.
 26. The polymericdevice material of claim 25 wherein for the macromer of formula [3c]:e=5-30; X=—O—; Y=(CH₂CH₂O)_(d)CH₃; q=4-15; T, T′independently=O(CH₂)_(d′), O(CH₂)_(d′)C₆H₄, or nothing; and L=H,—CH₂C(O)C₆H₅, —CH₂C(O)C₆H₄OCH₃, or —CH₂CH═CH₂;
 27. The polymeric devicematerial of claim 22 wherein the monomer of formula [1] is selected fromthe group consisting of benzyl methacrylate; 2-phenylethyl methacrylate;3-phenylpropyl methacrylate; 4-phenylbutyl methacrylate; 5-phenylpentylmethacrylate; 2-phenoxyethyl methacrylate; 2-(2-phenoxyethoxy)ethylmethacrylate; 2-benzyloxyethyl methacrylate;2-(2-(benzyloxy)ethoxy)ethyl methacrylate; 3-benzyloxypropylmethacrylate; benzyl acrylate; 2-phenylethyl acrylate; 3-phenylpropylacrylate; 4-phenylbutyl acrylate; 5-phenylpentyl acrylate;2-phenoxyethyl acrylate; 2-(2-phenoxyethoxy)ethyl acrylate;2-benzyloxyethyl acrylate; 2-(2-(benzyloxy)ethoxy)ethyl acrylate; and3-benzyloxypropyl acrylate.
 28. The polymeric device material of claim22 wherein the monomer of formula [2] is selected from the groupconsisting of ethylene glycol dimethacrylate; diethylene glycoldimethacrylate; triethylene glycol dimethacrylate; 1,6-hexanedioldimethacrylate; 1,4-butanediol dimethacrylate; 1,4-benzenedimethanoldimethacrylate; ethylene glycol diacrylate; diethylene glycoldiacrylate; triethylene glycol diacrylate; 1,6-hexanediol diacrylate;1,4-butanediol diacrylate; and 1,4-benzenedimethanol diacrylate.
 29. Thepolymeric device material of claim 22 wherein the amount of monomer [1]is 80 to 95% (w/w).
 30. The polymeric device material of claim 22wherein the amount of monomer [2] is 0.5 to 3% (w/w).
 31. The polymericdevice material of claim 22 wherein the amount of hydrophilic side-chainmacromer is 1 to 10% (w/w).
 32. The polymeric device material of claim31 wherein the amount of hydrophilic side-chain macromer is 1 to 5%(w/w).
 33. The polymeric device material of claim 32 wherein the amountof hydrophilic side-chain macromer is 2 to 4% (w/w).
 34. The polymericdevice material of claim 22 further comprising an ingredient selectedfrom the group consisting of a polymerizable UV absorbers and apolymerizable colorants.
 35. The polymeric device material of claim 34comprising 0.1-5% (w/w) of a polymerizable UV absorber and 0.01-0.5%(w/w) of a polymerizable colorant.
 36. An ophthalmic orotorhinolaryngological device comprising the polymeric device materialof claim 22 wherein the ophthalmic or otorhinolaryngological device isselected from the group consisting of intraocular lenses; contactlenses; keratoprostheses; corneal inlays or rings; otologicalventilation tubes; and nasal implants.
 37. The ophthalmic orotorhinolaryngological device of claim 36 wherein the ophthalmic orotorhinolaryngological device is an intraocular lens.